Sibon group

The Sibon’s group focus is to understand Coenzyme A metabolism in health and disease. Coenzyme A is a central metabolic cofactor, known for over 60 years. In recent years, the awareness is increasing that Coenzyme A, in addition to its essential role in metabolism also plays a role in signal transduction, ageing, epigenetics and neurodegeneration.

The current view is that cells obtain their Coenzyme A via a de novo biosynthesis pathway starting with the uptake of vitamin B5. Recently the Sibon group showed that cells and organisms can also take up Coenzyme A from external sources. The mechanism behind this newly discovered manner of obtaining Coenzyme A is under investigation. The presence of this alternative route of intracellular Coenzyme A is of high importance for subjects suffering from inborn genetic errors of impaired Coenzyme A de novo biosynthesis, resulting in severe neurodegenerative diseases. Findings obtained in model organisms are being explored how to use external supplies of Coenzyme A to develop therapies for these diseases.

Ody C.M. Sibon received her PhD in 1994 in Molecular Cell Biology at the University of Utrecht, The Netherlands. She studied the topological organization of transcription and splicing at the ultrastructural level under the supervision of Prof. A.J. Verkleij. She then moved to the United States, were she studied the role of DNA checkpoint regulation during early embryonal development in Drosophila melanogaster at the University of Stoney brook, NY. Her postdoctoral advisor was prof. W.E. Theurkauf.

In 1998 she moved to the University of Groningen, the Netherlands were she started her own group. In 2002 she received a VIDI grant and in 2011 a VICI grant, both from the Dutch organization for Scientific research. Her research now is focussed on understanding the mechanisms of an altered Coenzyme A uptake route and the possibilities of this route in health and disease. She is named as inventor on several patents based on her discoveries related to Coenzyme A metabolism and she is developing these further towards therapies for Coenzyme A-related diseases. In 2009 she became a full professor. She is partner and/or coordinator of several European, American and Dutch grants.

Chorea-Acanthocytosis is a rare neurodegenerative disorder which leads to degeneration in the central nervous system and movement disorders. It is caused by dysfunction of the VPS13A gene. How VPS13A dysfunction leads to Chorea-Acanthocytosis is not known. The goal of this project was to investigate the physiological role of VPS13A by using the common fruit fly, Drosophila …

In the past decades advances in medicine have led to an extended life span of the general population, which, as a negative consequence, increased the occurrence of age-related neurodegenerative diseases. The necessity to improve the quality of life together with the urge to decrease the economic burden related to patients with neurodegenerative diseases, brings focus to the …

Pantothenate kinase-associated neurodegeneration (PKAN, OMIM 234200) is an autosomal recessive, progressive neurodegenerative disorder. PKAN is caused by mutations in pantothenate kinase 2 (PANK2), the gene that encodes an enzyme (PANK2) which is a rate limiting enzyme in de novo Coenzyme A (CoA) biosynthesis. Interestingly, in humans there are four highly homologous PANK ge…

Post doctoral fellow position available at the Sibon lab for the following project on the intersection between chemistry and cell biology (pdf). Application at the end of this page.

Coenzyme A is an essential metabolic cofactor for living organisms and is mostly known for its role in over 100 cellular metabolic reactions. We and others demonstrated that Coenzyme A is also a key factor in protein modifications and signal transduction, further expanding the prominence of Coenzyme A in living organisms.
Until very recently, the consensus has been that intracellular Coenzyme A is obtained exclusively by a universally conserved five-step, de novo biosynthesis pathway in the cytosol of each cell, which begins with the uptake of vitamin B5. Patients with an inborn-error of this pathway suffer from neurodegeneration. Recently, we have demonstrated that cells and organisms have an alternative strategy for obtaining Coenzyme A, which involves the uptake of extracellular Coenzyme A. In particular, we have shown that various eukaryotic cells and organisms convert Coenzyme A present in the environment extracellularly into 4’-phosphopantetheine. This metabolite is subsequently incorporated into cells and converted back into Coenzyme A. This project is aimed to investigate the physiological relevance of this discovery.
Preliminary results using validated fruit fly models suggest a possible flow of Coenzyme A (precursors) between organisms, namely from mothers to progeny or from microflora to the host.
By using these models and newly developed sensitive analytical detection methods for Coenzyme A and its precursors, the project aims to provide proof for intra-organismal flows of Coenzyme A. This research will change longstanding Coenzyme A concepts with possible impact on health and disease, especially for the treatment of inborn-errors of Coenzyme A biosynthesis.

Position for 1 year with an extension of another 2 years.
Candidates much have obtained their PhD and must have a strong publication record. A background in chemistry is preferable but not a requirement.

Information: Ody Sibon: o.c.m.sibon@umcg.nl

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Post doc position Sibon Lab

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